title: The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury.
abstract: BACKGROUND
  Notch signaling plays a critical role in the maintenance of intestinal crypt epithelial cell proliferation. The aim of this study was to investigate the role of Notch signaling in the proliferation and regeneration of intestinal epithelium after intestinal ischemia reperfusion (I/R) injury.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to sham operation or I/R by occlusion of the superior mesenteric artery (SMA) for 20 min. Intestinal tissue samples were collected at 0, 1, 2, 4, and 6 h after reperfusion. Proliferation of the intestinal epithelium was evaluated by immunohistochemical staining of proliferating nuclear antigen (PCNA). The mRNA and protein expression levels of Notch signaling components were examined using Real-time PCR and Western blot analyses. Immunofluorescence was also performed to detect the expression and location of Jagged-2, cleaved Notch-1, and Hes-1 in the intestine. Finally, the γ-secretase inhibitor DAPT and the siRNA for Jagged-2 and Hes-1 were applied to investigate the functional role of Notch signaling in the proliferation of intestinal epithelial cells in an in vitro IEC-6 culture system.
  
  
  RESULTS
  I/R injury caused increased intestinal crypt epithelial cell proliferation and increased mRNA and protein expression of Jagged-2, Notch-1, and Hes-1. The immunofluorescence results further confirmed increased protein expression of Jagged-2, cleaved Notch-1, and Hes-1 in the intestinal crypts. The inhibition of Notch signaling with DAPT and the suppression of Jagged-2 and Hes-1 expression using siRNA both significantly inhibited the proliferation of IEC-6 cells.
  
  
  CONCLUSIONS
  The Jagged-2/Notch-1/Hes-1 signaling pathway is involved in intestinal epithelium regeneration early after I/R injury by increasing crypt epithelial cell proliferation.
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qiu
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Wensheng
authors.initials: W
authors.lastname: Wang
authors.forename: Weidong
authors.initials: W
authors.lastname: Xiao
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Songwei
authors.initials: S
authors.lastname: Yang
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
authors.forename: Yuanhang
authors.initials: Y
authors.lastname: Ma
authors.forename: Dingsong
authors.initials: D
authors.lastname: Lu
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D000072101:Jagged-2 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000235:genetics; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004151:Dipeptides; D018398:Homeodomain Proteins; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C490502:Jag2 protein, rat; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester